Regulation of Homologous Recombination by RNF20-Dependent H2B Ubiquitination
Regulation of Homologous Recombination by RNF20-Dependent H2B Ubiquitination
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DOI：
10.1016/j.molcel.2011.02.002
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发表时间：
2011-03-04
期刊：
影响因子：
16
通讯作者：
Komatsu, Kenshi
中科院分区：
文献类型：
--
作者：
Nakamura, Kyosuke;Kato, Akihiro;Komatsu, Kenshi
E3泛素连接酶RNF20通过在转录中单泛素化组蛋白H2B来调节染色质结构。在这里，我们表明，RNF20是本地化的双链DNA断裂（DSB）独立的H2AX和所需的DSB诱导的H2B泛素化。此外，RNF20是DSB处H3K4甲基化和染色质重塑因子SNF2h募集所必需的。RNF20的缺失、SNF2h的缺失或缺乏泛素化位点（K120R）的H2B突变体的表达损害了DNA末端的切除和RAD 51和BRCA 1的募集。因此，缺乏RNF20或SNF2h的细胞和表达H2B K120R的细胞在同源重组修复（HRR）中表现出明显的缺陷和对辐射的敏感性增强。最后，RNF20在HRR中的功能可以通过强迫染色质松弛而部分绕过。因此，RNF20介导的H2B泛素化在DSB中通过染色质重塑在HRR中起关键作用。
The E3 ubiquitin ligase RNF20 regulates chromatin structure by monoubiquitinating histone H2B in transcription. Here, we show that RNF20 is localized to double-stranded DNA breaks (DSBs) independently of H2AX and is required for the DSB-induced H2B ubiquitination. In addition, RNF20 is required for the methylation of H3K4 at DSBs and the recruitment of the chromatin-remodeling factor SNF2h. Depletion of RNF20, depletion of SNF2h, or expression of the H2B mutant lacking the ubiquitination site (K120R) compromises resection of DNA ends and recruitment of RAD51 and BRCA1. Consequently, cells lacking RNF20 or SNF2h and cells expressing H2B K120R exhibit pronounced defects in homologous recombination repair (HRR) and enhanced sensitivity to radiation. Finally, the function of RNF20 in HRR can be partially bypassed by forced chromatin relaxation. Thus, the RNF20-mediated H2B ubiquitination at DSBs plays a critical role in HRR through chromatin remodeling.